The invention relates to novel steroids with radical-attracting aromatic substituents, processes for their production, and medications containing these compounds for the prophylaxis and therapy of radical-mediated cell damage.
From professional and patent literature it is known that reactive oxygen species (ROSs), free oxygen radicals and other radial forms play an important role in the occurrence of many kinds of cell damage, such as ischemic and traumatic organ injuries, and inflammatory and toxic processes.
A negative effect of ROSs, free oxygen radicals and other forms of radicals can also be found in brain and spinal column injuries, shock states, stroke, muscular dystrophy, emphysemas, adult respiratory distress syndrome (ARDS), asthma, aging processes, in tissue damage after myocardial infarction, damage from toxic processes and radiation, burns, and transplant-dictated immune reactions. Among other factors, lipid peroxidation and the oxidation of low-density lipoprotein (LDL) cholesterol, combined with irreversible membrane and endothelial damage are the starting point for such radical-mediated cell damage.
It is also known that lipophilic substances, such as lipophilic steroids, with radical-scavenging ("radical-trapping") properties can be suitable for prophylaxis and therapy of radical-mediated cell damage.
Unlike the known low-molecular phenolic antioxidants, these lipophilic steroids are transported with a certain selectivity into the region of the cell membrane or endothelium, where they can develop their efficacy.
The therapeutic utility is determined by the action spectrum of the respective substance.
International Patents WO 87/01716 and WO 91/11453, European Patents EP 0 389 368, EP 0 389 369, and EP 0 389 370, and French Patent FR 2 640 977, for instance, describe steroids with scavenger properties.
WO 87/01716, WO 91/11453 and EP 0 389 368/. . . 369/. . . 370 describe steroids which a the terminal carbon atom of the C.sub.17 side chain contain an amino group, which can be substituted or can be a component of a heterocyclic ring system.
In FR 2 640 977, a structural type is shown that has a substituted phenyl ring in the .beta. position on the C.sub.11 atom.
It is shown in J. Phys. Org. Chem. 3 (1990), 309-315 that estrogens, and especially catechol estrogens, can act as radical catchers. Estradiol, estrone, estriol and 2-hydroxyestradiol inhibit peroxidation in vitro and in vivo.